Acne is a common inflammatory disease of human skin, and concentrates in skin areas where sebaceous glands are largest, most numerous, and most active. In its milder types, it is a more or less superficial disorder which is evidenced by slight, spotty irritations and ordinary skin hygiene is a satisfactory treatment. However, in the more inflammatory types of acne, bacterial invasion of or about the pilosebaceous follicles occurs and pustules, infected cysts and, in extreme cases, canalizing inflamed and infected sacs appear. These lesions may become extensive and leave permanent, disfiguring scars.
To reduce the severity of acne, various forms of medication have previously been topically applied to the skin. Antibacterial soaps have been used as well as bactericidal agents such as sulfur and resorcinol. Other topical compositions have separately contained benzoyl peroxide, hexachlorophene, erythromycin or neomycin sulfate. None of these prior preparations has been completely effective.
As disclosed by Klein et al. (U.S. Pat. No. 4,497,794), it was discovered that a mixture on the skin of a peroxide, especially benzoyl peroxide and an antibiotic or antibacterial such as clindamycin, neomycin, sodium sulfacetamide, sulfur, tetracycline or erythromycin is particularly beneficial as they can exert a statistically significant synergistic effect. Peroxides inhibit the formation of free fatty acids in the skin, primarily through inactivation of extracellular lipase (via oxidation) necessary to cleave triglycerides into free fatty acids and glycerol. The antibiotic or antibacterial component reduces the concentration of Corynebacterium acnes (i.e., P. acnes), a normal anaerobic bacteria which is the prime source of the lipase. Instead of the benzoyl peroxide, which is preferred, peroxides such as stabilized hydrogen peroxide and peroxides of organic acids, such as a lauroyl peroxide, may be used.
As disclosed by Klein et al., erythromycin and benzoyl peroxide may be applied to the skin in combination in a preformulated aqueous gel. However, the premix must be used relatively promptly due to the chemical incompatibility of the two active agents. Because of this, it is advisable that the two agents be put in separate vials, bottles or other containers. For example, the Klein et al. patent discloses a kit containing, separately bottled compositions comprising benzoyl peroxide and erthyromycin dissolved in ethanol or acetone. However, separately packaging multiple dosages of the two active ingredients presents a number of disadvantages to the end-user. For example, the pharmacist must compound each prescription refill. This is both time consuming and provides opportunity for spillage, or over- or underdosing. In addition, this pharmacy-compounded system adds cost to the end-user.
Therefore there is a need to develop a method of packaging and delivering of chemically incompatible dermatological agents. To this end, several applicator systems have been developed with a prescored fracture line in one surface of a package which separates the agents in discrete portions of a single package. For example, U.S. Pat. No. 4,140,409 to DeVries discloses a package system for containing and dispensing liquids and other flowable materials comprising a reservoir chamber in each half of an elongated package. A prescored fracture line in one surface of the package ruptures when the ends of the package are urged together, and the contents of the chambers are expelled into an applicator sponge that is attached to the outside of the package. However, a disadvantage of packages with such externally placed applicators is that the applicator may become soiled or detached. Also, where a sterile applicator is desired, such a package system may not maintain the applicator under sanitary conditions prior to use.
Recently, Smith et al. (U.S. Pat. No. 5,242,433) have disclosed an applicator system comprising at least two absorbent pads which are each impregnated with a different dermatological composition, and which are packaged separately in a side-by-side manner, attached to a moisture-impermeable base sheet. When the cover sheet is removed, the pads can be wiped onto the skin of the user, simultaneously releasing and combining the compositions from the pads. However, the construction and loading of this system is relatively complex, requiring that the pads be separately attached to the base sheet impregnated with the compositions, and then covered with a moisture impermeable seal.
Therefore, there is a need for a method of dispensing system which addresses the above mentioned problems of prior dispensing systems. In particular, there is a need for a packaging system for dispensing active ingredients, which has an improved configuration for releasing the contents of the packaging and that is not prone to premature mixture, but provides ready dispensing of the package contents. There is also a need for a packaging that is a convenient means of dispensing a plurality of active ingredients from multiple chambers within the packaging system to overcome the physical or chemical incompatibility of the substances.